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Original Research: Sleep Disorders |

Hypertension Is Associated With Undiagnosed OSA During Rapid Eye Movement Sleep FREE TO VIEW

Sarah L. Appleton, PhD; Andrew Vakulin, PhD; Sean A. Martin, PhD; Carol J. Lang, PhD; Gary A. Wittert, MD; Anne W. Taylor, PhD; R. Doug McEvoy, MD; Nick A. Antic, MBBS, PhD; Peter G. Catcheside, PhD; Robert J. Adams, MD, MBBS
Author and Funding Information

FUNDING/SUPPORT: This study was funded by a National Health and Medical Research Council of Australia Project Grant (627227). Financial support for the conduct of sleep studies was also obtained from the ResMed Foundation, La Jolla, California.

aThe Health Observatory, Discipline of Medicine, University of Adelaide, The Queen Elizabeth Hospital Campus, Woodville, SA, Australia

bFreemasons Foundation Centre for Men’s Health, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia

cAdelaide Institute for Sleep Health, a Flinders Centre of Research Excellence, School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia

dSleep and Respiratory Medicine, Repatriation General Hospital, Southern Adelaide Local Health Network, Daw Park, SA, Australia

eThe NHMRC Centres of Research Excellence, CIRUS and NEUROSLEEP, Woolcock Institute of Medical Research, Central Clinical School, University of Sydney, NSW, Australia

fPopulation Research & Outcomes Studies, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia

CORRESPONDENCE TO: Sarah Appleton, PhD, Discipline of Medicine, The University of Adelaide, Queen Elizabeth Hospital, Woodville Rd, Woodville, SA, 5011, Australia


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):495-505. doi:10.1016/j.chest.2016.03.010
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Background  Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension.

Methods  The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded ≥ 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up [range, 48-74]) in men free of hypertension at baseline.

Results  Severe REM OSA (apnea hypopnea index ≥30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 [1.04-4.81]). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) ≥ 20/h was significantly associated with prevalent hypertension (2.67 [1.33-5.38]) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 [0.79-6.84]). Similar results were seen when analyses were confined to men with non-REM AHI < 10.

Conclusions  In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed.

Figures in this Article

OSA and hypertension commonly occur together., Cross-sectional studies show hypertension is present in at least 60% of people with moderate to severe OSA, and OSA occurs in 70% to 85% of patients with resistant hypertension., Mechanisms linking OSA to hypertension development may include intermittent hypoxemia-induced sympathetic activation, endothelial dysfunction, and systemic inflammation.

FOR EDITORIAL COMMENT SEE PAGE 475

However, evidence from longitudinal studies linking OSA with hypertension is conflicting.,,, Although an increased risk of hypertension from OSA was observed in the Wisconsin Sleep Cohort Study, the Sleep Heart Health Study, and the Vitoria Sleep Cohort found the relationship was not significant when adjusted for BMI and age. Evidence from clinical cohorts suggests that OSA is a risk factor for the development of hypertension, but these studies have an increased risk of referral bias. Although treatment of OSA with CPAP therapy appears beneficial for hypertension, the magnitude of effect is modest., Recent reports from an extended follow-up of the Wisconsin Sleep Cohort found OSA during rapid eye movement (REM) sleep was independently associated with prevalent and incident hypertension and incident nondipping nocturnal BP, but independent relationships with OSA during non-REM (NREM) sleep were not seen. This is significant because REM sleep is associated with higher sympathetic activity compared with NREM sleep, with increased heart rate, BP, and myocardial metabolic demand. Also, obstructive events during REM sleep tend to be longer, with greater oxygen desaturations and increases in heart rate and BP than those during NREM sleep. However, further work is needed before it can be concluded that hypertension is related to OSA occurring only in REM sleep.

Our aim was to determine temporal associations of previously unrecognized/undiagnosed sleep apnea with hypertension and to identify relationships with REM OSA. We examined data from a comprehensively characterized representative cohort of men aged > 40 years in South Australia.

Study Participants

The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study includes randomly selected community dwelling men aged at least 35 years at baseline (2002-2006) and of largely Australian or European descent (96%) as previously described. Data for the current analyses were derived from MAILES 1 (2002-2006) and MAILES 2 (2007-2010) biomedical clinic assessments, the MAILES 3 follow-up computer-assisted telephone interview (August 2010), and a substudy of home-based polysomnography studies in 2010 and 2011 (Fig 1). Approval for the MAILES study was obtained from the Human Research Ethics Committees of the North West Adelaide Health Service (approval no. 2010054). All participants gave written informed consent.

Figure 1
Figure Jump LinkFigure 1 Flow diagram of the MAILES study. MAILES = Men Androgens Inflammation Lifestyle Environment and Stress; REM = rapid eye movement.Grahic Jump Location
Sleep Data

Previously diagnosed OSA (n = 184) was identified in the MAILES computer-assisted telephone interview (n = 1,629) by a “yes” response to “Have you ever been diagnosed with obstructive sleep apnea with a sleep study?” Men reporting “no” (n = 1,445) were invited to undergo a sleep study, with 75.2% agreeing. In 2010 to 2011, 857 participants underwent eight-channel in-home unattended polysomnography (Embletta X100, Embla Systems) to measure EEG, EOG, electromyelography, nasal pressure, thoracic and abdominal effort, oximetry, and body position. Trained staff visited study participants in their homes to set up and attach the sleep study equipment, administer the Epworth Sleepiness Scale, undertake anthropometry, and record current medications. Failed studies (n = 40) were repeated, generating a final sample of 837.

A single experienced sleep technician performed manual scoring of all home polysomnographies (PSGs) according to 2007 American Academy of Sleep Medicine (AASM) alternative criteria. Acceptable studies had 3.5 h of sleep and 5.5 h of total recorded study time. Apneas were defined as complete cessations of airflow, measured using nasal pressure, lasting ≥ 10 s. Hypopnea was a > 50% decrease in nasal pressure (or in both thoracic and abdominal excursions) with an associated ≥ 3% oxygen desaturation or an EEG arousal. OSA was defined as an apnea hypopnea index (AHI) ≥ 10/h of sleep, with further categorization: mild, AHI of 10 to 19/h; moderate, 20 to 29/h; and severe, ≥ 30/h. The 2007 AASM alternative criteria were used as these were recommended for use in prospective epidemiological studies by the AASM and by an expert panel of the Australasian Sleep Association. The cutoffs for classification were chosen because Ruehland et al have shown that an AHI of 5/h of sleep used to define sleep disordered breathing scored by the “recommended” AASM criteria is equivalent to an AHI of 10/h of sleep using the alternate AASM definition, and 15/h using the older 1999 criteria. To maintain comparability with previous work, a cutoff of 10/h was chosen. To ensure precision, analysis of REM OSA was conducted in 739 men (mean REM sleep = 60 min) after exclusion of 98 men with < 30 min recorded REM sleep (mean = 19 min). REM OSA was defined as an AHI (AHIREM) ≥ 10/h of REM sleep, with severity categorized as discussed previously. REM-only OSA was also identified by AHI ≥ 10/h of REM sleep in those with AHI < 10/h of NREM sleep. Nocturnal hypoxemia was identified by the 3% oxygen desaturation index (ODI 3%) and the percentage of sleep time with oxygen saturation < 90% (TST90).

Chronic Conditions

MAILES 1 and 2 study clinic assessments included BP, anthropometry and a fasting blood sample was drawn for glucose, and lipid measurements. BP was calculated as the mean of two measures, taken 5 to 10 min apart using a standard, calibrated sphygmomanometer (Mercurial, Accoson), when the participant was relaxed and seated. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg or medication use. Prevalent hypertension was defined as hypertension at the MAILES 2 clinic assessment. Recent-onset hypertension was defined as hypertension at MAILES 2 in those without hypertension or cardiovascular disease (CVD, determined by self-reported doctor diagnosed myocardial infarction, angina, stroke, or transient ischemic attack) at the MAILES 1 baseline assessment. Diabetes was defined as self-reported doctor diagnosis, fasting plasma glucose ≥ 7.0 mmol/L, glycated hemoglobin ≥ 6.5%, or diabetes medication use.

Statistical Analysis

Data were analyzed using the IBM SPSS, version 20.0 (IBM Corporation). Univariate associations of prevalent and recent-onset hypertension with different follow-up PSG indices were determined with χ2 tests. Logistic regression analyses identified (1) associations of prevalent hypertension with OSA and polysomnographic indices adjusted for MAILES 2 variables associated with hypertension in univariate analyses, using P values < .25 including age, waist circumference, smoking history, alcohol use, usual sleep hours, quartiles of percentage supine sleep time; and (2) associations of recent-onset hypertension with OSA and polysomnographic indices adjusted for baseline (MAILES 1) variables including age, waist circumference, smoking history, alcohol use, and weight gain over the follow-up period. Analyses to determine relationships between REM OSA and hypertension were additionally adjusted for log-transformed NREM AHI (AHINREM). To remove the contribution of OSA occurring during NREM sleep, we conducted analyses in men without OSA (AHI < 10/h and AHINREM < 10/h). Adjusted analyses were conducted with BMI used in place of waist circumference which did not change the findings. Given that evidence suggests that indices of abdominal adiposity are better are better discriminators of cardiovascular risk factors than BMI, only the models with adjustment for waist circumference are reported. P values less than .001 that are unable to be calculated by SPSS are presented as P < .01.

Of 739 men with valid PSG data and ≥ 30 min of REM sleep, data on hypertension or treatment from the MAILES 2 clinic were available in 715 men (97%). Prevalent hypertension occurred in 390 (54.5%) participants aged > 40 years. Of 351 men who were free of hypertension and CVD at baseline, hypertension developed in 99 men (28%) over the mean follow-up time of 56 months (SD = 5; range, 48-74 months).

Clinical characteristics of the sample with ≥ 30 min of REM sleep and those with hypertension are shown in Table 1. Prevalent hypertension showed significant associations with age, obesity, moderate- to high-risk alcohol consumption, diabetes, and CVD. The recent onset of hypertension was also related to increasing age, obesity, diabetes at baseline, and weight gain over the follow-up period.

Table Graphic Jump Location
Table 1 Biomedical Characteristics, % (No.), of Study Participants With at Least 30 Min of REM Sleep Overall and by Prevalent and Recent-Onset Hypertension

Demographic characteristics of participants by REM AHI and total AHI categories are shown in Table 2. Increasing severity of OSA and REM OSA were associated with increasing age and reduced participation in the workforce.

Table Graphic Jump Location
Table 2 Demographic Characteristics of Participants and by AHI Severity Category Overall and During REM Sleep

AHI = apnea hypopnea index; REM = rapid eye movement; UK = United Kingdom.

PSG and sleep characteristics of men with ≥ 30 min of REM sleep overall and with hypertension are shown in Table 3. In univariate analysis, prevalent hypertension showed significant associations with OSA (REM and NREM), mean oxygen desaturation (REM and NREM), and nocturnal hypoxemia (ODI 3% and TST90), but not excessive daytime sleepiness or snoring. Relationships of prevalent hypertension with mean percentage time in REM sleep and the lowest quartile of percentage time in supine sleep position were also seen that were of borderline significance. Recent-onset hypertension was associated with OSA (REM and NREM), mean oxygen desaturation (REM and NREM), ODI 3%, and TST90.

Table Graphic Jump Location
Table 3 Sleep Study Characteristics, % (No.), of Study Participants With at Least 30 Min of REM Sleep Overall and by Prevalent and Recent-Onset Hypertension
a Epworth Sleepiness Scale > 10.

TST90 quartiles: 25th, 0.056%; 50th, 0.691%; 75th, 3.874%. ODI 3% quartiles: 25th, 3.7665; 50th, 8.2894; 75th, 16.3338. % total time in supine position quartiles: 25th, 6.82%; 50th, 22.66%; 75th, 43.7%. NREM = non-rapid eye movement; ODI 3% = oxygen desaturation index (≥ 3% desaturation events/h of sleep); TST90 = percentage time of sleep time spent with oxygen saturation < 90%. See Table 2 legend for expansion of other abbreviations.

Table 4 shows associations of REM OSA and hypertension overall and in men with AHI < 10 and NREM AHI < 10. Overall, prevalent and recent-onset hypertension were independently associated with severe REM OSA (and AHIREM ≥ 20) after adjustment for confounders including AHINREM. These associations were not attenuated by the addition of AHINREM and log-transformed AHINREM showed no significant association with prevalent (OR, 1.11; 95% CI, 0.93-1.33) or recent-onset hypertension (OR, 1.04; 95% CI, 0.80-1.35).

Table Graphic Jump Location
Table 4 Prevalent and Recent-Onset Hypertension, % (No.), in Relation to REM OSA Overall and in Men Without OSA (AHI < 10, AHINREM < 10) and OR, 95% CI for Hypertension Associated With REM OSA Severity
a Adjusted for age, waist circumference, smoking, alcohol, sleep hours, quartiles of percentage time in supine sleep position, AHINREM.
b Adjusted as for first modela without AHINREM.
c Adjusted for baseline age, waist circumference, smoking, alcohol, AHINREM, and weight gain over the follow-up period.
d Adjusted as for third modelc without AHINREM.

P presented for distribution of hypertension across REM OSA categories by χ2 linear by linear association. AHINREM = apnea hypopnea index for non-REM. See Table 2 legend for expansion of other abbreviations.

In analyses restricted to men with an overall AHI <10/h (n = 352), moderate-severe REM OSA (AHIREM ≥ 20/h) occurred in 56 (15.4%). Prevalent and recent-onset hypertension were more common in moderate-severe REM OSA (Table 4). In adjusted analyses, prevalent hypertension was significantly associated with AHIREM ≥ 20/h. Of 207 men with AHI < 10/h and without hypertension at baseline, hypertension developed in 49 men. Logistic regression showed positive, but non-significant associations of recent-onset hypertension with AHIREM ≥ 20/h.

The relationship of hypertension with REM OSA was also examined in men with AHINREM < 10 (n = 383) consistent with the analysis conducted in the Wisconsin cohort (Table 4). AHIREM ≥ 10 was found to be present in 182 men (47.5%), and AHIREM 20 to 29/h and ≥ 30/h occurred in 14.9% (n = 57) and 5.7% (n = 22), respectively. Prevalent hypertension and recent-onset hypertension were more common in men with AHIREM ≥ 20/h, but a significant relationship with only prevalent hypertension remained after adjusting for confounders.

In all three models for prevalent hypertension (all men, AHI < 10, and NREM AHI < 10), no adjusted associations were seen with increasing quartiles of percentage sleep time spent in supine position.

The association of hypertension with measures of nocturnal hypoxemia was also assessed in multivariable models. Mean REM oxygen desaturation was significantly associated with prevalent hypertension (OR, 1.26 [95% CI, 1.08-1.47]; P = .004) independent of mean NREM oxygen desaturation and % sleep time in supine position. NREM mean oxygen desaturation showed no significant associations with prevalent hypertension (OR, 1.09 [95% CI, 0.86-1.37]; P = .48). A significant adjusted association of mean REM oxygen desaturation with recent-onset hypertension (OR, 1.32 [95% CI, 1.08-1.62]; P = .007) was attenuated to borderline significance (OR, 1.25 [95% CI, 0.99-1.57]; P = .06) after inclusion of mean NREM oxygen desaturation in the model (OR, 1.21[95% CI, 0.84-1.73]; P = .30).

Furthermore, compared with the lowest quartile, the third (OR, 1.57 [95% CI, 1.00-2.44]) and fourth quartiles of TST90 (OR, 2.26 [95% CI, 1.40-3.66]) were independently associated with prevalent but not recent-onset hypertension, and the second (OR, 1.94 [95% CI, 1.26-3.00]), third (OR, 2.17 [95% CI, 1.38-3.41]), and fourth quartiles of ODI 3% (OR, 2.65 [95% CI, 1.65-4.24]) were independently associated with prevalent hypertension. A borderline association of the highest ODI quartile with recent-onset hypertension was also seen (OR, 1.90 [95% CI, 0.96-3.78], P = .067).

Analyses were also conducted in all men (n = 810) to retain 98 men with < 30 min of REM sleep. Of these men with < 30 min REM sleep, 23.5% demonstrated severe OSA and 36.7% also had no evidence of OSA. Prevalent hypertension occurred in 448 (55.3%) participants aged > 40 years. Of 391 men who were free of hypertension and CVD at baseline, hypertension developed in 110 men (28%) over the mean follow-up time of 56 months (SD = 5; range, 48-74 months). Clinical and sleep characteristics of the sample and those with prevalent and recent onset hypertension are shown in e-Tables 1 and 2, respectively, and are similar to those seen in the sample of men with ≥ 30 min of REM sleep. Prevalent and recent-onset hypertension increased with OSA severity (Table 5). In logistic regression analyses, prevalent but not recent-onset hypertension was associated with moderate and severe categories of OSA.

Table Graphic Jump Location
Table 5 Prevalent and Recent-Onset Hypertension, % (No.), in Relation to Severity of OSA and OR, 95% CI for Hypertension Associated With OSA Severity
a Pearson χ2.
b χ2 linear by linear association.
c Adjusted for age, waist circumference, smoking, alcohol, and supine sleep position.
d Adjusted for baseline age, waist circumference, smoking, alcohol, and weight gain over the follow-up period.

See Table 2 legend for expansion of abbreviation.

In an unselected urban population of men with no previous diagnosis of OSA, moderate-severe OSA during REM sleep was independently associated with prevalent and recent-onset hypertension. The relationship with prevalent hypertension persisted in men not considered to have OSA (AHI < 10 and AHINREM < 10). Hypertension showed no significant association with NREM AHI or sleep posture; furthermore, measures of nocturnal hypoxemia, including oxygen desaturation during REM sleep, also showed independent relationships with prevalent hypertension.

Evidence from population-based studies reporting total AHI is conflicting,,, with some studies finding that the relationship between OSA and incident hypertension is largely confounded by obesity and age. Older age, obesity, and weight gain were also important confounders in our observed relationship between recent-onset hypertension and OSA when total AHI was considered. However, our data support recent findings from the Wisconsin Sleep Cohort, in which REM OSA was independently associated with prevalent and incident hypertension. To allow adequate observation of REM sleep and to be consistent with the analysis by Mokhlesi and colleagues, we excluded subjects with less than 30 min of REM sleep from the REM OSA-specific analyses. Although this may exclude those at greatest risk of hypertension (ie, those with severe OSA or REM OSA whose high frequency of OSA arousals during the REM period result in very short REM sleep), this group remained in the analysis of hypertension in relation to all OSA.

We found a stronger association between hypertension and REM OSA than Mokhlesi et al when they studied the entire Wisconsin cohort, where the association was only marginal. This may be related to differences in the reference groups used. Mokhlesi et al used a reference category of AHI < 1 rather than < 5 events/h, which is the standard criterion according to the “recommended” scoring criteria for assessing the presence of OSA and related risks and corresponds to our reference category AHI < 10 with the 2007 AASM “alternate” scoring criteria., This emphasizes the need to (1) establish biological plausibility of potential risks associated with very infrequent sleep-disordered breathing events and (2) investigate a threshold vs the continuum of OSA related risks (as has been demonstrated for example with hypertension and elevated cholesterol) for outcomes.

The level of oxygen desaturation that predisposes to cardiovascular risk is unclear given that in the Sleep Heart Health Study only hypopneas with a desaturation of at least 4%, but not milder desaturations, were associated with CVD. Dean at al also recently reported from the Multi-Ethnic Study of Atherosclerosis that hypopneas with a ≥ 4% desaturation were most consistently associated with systolic and diastolic BP. In the Wisconsin Study, hypopneas were scored based on oxygen desaturations of at least 4%. Our study scored hypopneas consistent with the current AASM recommendation of ≥ 3% arterial oxygen desaturations. Desaturations of 3% are more common and this criterion results in a doubling or more of the AHI compared with the 4% criterion. The significance for population health is that the size of the OSA population identified as potentially at risk is considerably greater using more liberal hypopnea criteria. Recent data from the Wisconsin cohort provide modeled estimates of moderate to severe OSA 13% in men (30-70 years). This contrasts with rates of moderate-severe OSA in men (≥ 40 years) of 26% in our study and 50% in the recent HypnoLaus Study, in which hypopneas were scored with the 2012 AASM criteria of 30% airflow reduction/3% desaturation or an arousal. Importantly, a relationship of AHI ≥ 20/h with prevalent hypertension was also demonstrated in the HypnoLaus study. Thus, use of different scoring criteria will result in significantly different AHI results within individuals and across populations, that may or may not affect associations with comorbidities including hypertension. Our findings indicate the scale of the problem of OSA and hypertension is considerable, and irrespective of the directionality of causal effects, health-care professionals should ensure that a patient presenting with one disorder is assessed for the other.

The significance of REM OSA is uncertain. REM OSA has also been shown to affect glycemic control in diabetes, but not quality of life. As previously noted,, CPAP usage of 3 to 4 h common to many users is unlikely to ameliorate the effects of REM OSA, which tends to occur in later cycles of sleep when CPAP is most likely to have been removed. This may largely account for the modest effects of CPAP on hypertension observed in randomized controlled trials. What constitutes adequate CPAP use varies between outcomes and 4 h of use that is adequate to treat daytime sleepiness is inadequate for the improvement of quality of life and possibly is also inadequate to reduce the burden of cardiometabolic outcomes including hypertension.

The pathophysiological mechanism by which REM OSA contributes to hypertension is unclear. Calandra-Buonaura et al point out strong overlap in respiratory and cardiovascular control circuits in the nucleus of the solitary tract and ventrolateral medulla, and postulate that hypertension in OSA reflects maladaptive autonomic neuroplasticity to episodic sympathetic activation to OSA events in sleep. In addition, more wakelike EEG and cardiovascular changes occur in REM than NREM sleep. Although speculative, a relationship between REM-OSA and hypertension could reflect a more REM-specific baroreflex control system vulnerability to respiratory disturbances in sleep via stronger wake-input involvement to cardiorespiratory control in REM than in NREM sleep.

This was not a prospective study of the development of hypertension in relation to OSA. Sleep studies were only available at follow-up, limiting us to examining cross-sectional and retrospective associations of OSA with hypertension development. The MAILES cohort is a longitudinal study of nontraditional predictors of CVD and diabetes outcomes in men including androgens; thus, the generalizability of our findings to women is unknown. However, women with REM OSA may be disproportionately affected by hypertension given that REM OSA occurs more commonly in women than in men. Sample size issues limited analyses of recent-onset hypertension in subgroups (eg, AHI < 10, AHINREM < 10). Nevertheless, we still observed significant associations in all men and consistent trends in subgroups.

In a community sample of middle-aged and older men without a diagnosis of OSA until the present study, severe REM OSA was independently associated with prevalent hypertension and the recent development of hypertension. These relationships were evident when hypopneas were defined by the current recommended 3% oxygen desaturation criterion. The implication for population health is the increased size of the population identified with the 3% criterion potentially at-risk of hypertension, because the only other previous study that identified this association defined hypopneas by a desaturation of at least 4%. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed.

Author contributions: S. A. takes responsibility for (is the guarantor of) the content of the manuscript, including the data and analysis. G. W., R. A., A. T., and S. A. contributed to the study design. A. V., S. M., and P. C. contributed to data collection. S. A. conducted the data analysis. S. A. and R. A. drafted the manuscript. All authors contributed to the interpretation of the data, critical revision of the final manuscript and approve the final version of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. A., A. V., C. L., D. M., N. A., P. C., A. T., and G. W. have received research funding from the National Health and Medical Research Council of Australia. R. A. received research funding from the ResMed Foundation, non-financial support from Embla Systems, Colorado. D. M. received research funding from the ResMed Foundation, Philips Respironics, Fisher and Paykel, equipment donations from ResMed, Philips Respironics, SomnoMed, and lecture fees from Philips Respironics. N. A. received research funding from Philips Respironics, and Fisher and Paykel, equipment donations from ResMed, Philips Respironics, SomnoMed, and lecture fees/payment for development of educational presentations from ResMed. P. C. received research funding from the Australian Research Council, equipment support from Philips Respironics, AirLiquide Healthcare. G. W. received research funding from Bayer Schering, Eli Lilly, ResMed Foundation, and Lawley Pharmaceuticals, non-financial support from Embla Systems, Colorado, and he has served on International Advisory Boards for Eli Lilly, Novo Nordisk, received speaking fees from Eli Lilly, Bayer Schering, Sanofi, Novo Nordisk, AstraZeneca, I-Nova, Elsevier. None declared (S. M., S. A.).

Role of the sponsors: The study sponsors had no role in the development of the research or the manuscript.

Additional information: The e-Tables can be found in the Supplemental Materials section of the online article.

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Findley L.J. .Wilhoit S.C. .Suratt P.M. . Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea. Chest. 1985;87:432-436 [PubMed]journal. [CrossRef] [PubMed]
 
Grant J.F. .Martin S.A. .Taylor A.W. .et al Cohort profile: the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study. Int J of Epidemiol. 2014;43:1040-1053 [PubMed]journal. [CrossRef]
 
Iber C. .Ancoli Israel S. .Chesson A. Jr..Quan S. . The AASM Manual for the Scoring of Sleep and Associated Events.  2007;:- [PubMed] American Academy of Sleep Medicine Westchester, ILjournal
 
ASTA/ASA. Commentary on AASM Manual for the Scoring of Sleep and Associated Events. December 2010.http://www.sleep.org.au/information/sleep-documents/astaasa-commentary-on-aasm-manual-for-scoring-of-sleep-associated-events-december-2010. Accessed December 1, 2016.
 
Ruehland W.R. .Rochford P.D. .O'Donoghue F.J. .Pierce R.J. .Singh P. .Thornton A.T. . The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index. Sleep. 2009;32:150-157 [PubMed]journal. [PubMed]
 
Mokhlesi B. .Punjabi N.M. . “REM-related” obstructive sleep apnea: an epiphenomenon or a clinically important entity? Sleep. 2012;35:5-7 [PubMed]journal. [PubMed]
 
Lee C.M.Y. .Huxley R.R. .Wildman R.P. .Woodward M. . Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol. 2008;61:646-653 [PubMed]journal. [CrossRef] [PubMed]
 
Peker Y. . REM sleep: a nightmare for patients with obstructive sleep apnea? Am J Respir Crit Care Med. 2014;190:1088-1090 [PubMed]journal. [CrossRef] [PubMed]
 
Punjabi N.M. .Newman A.B. .Young T.B. .Resnick H.E. .Sanders M.H. . Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas. Am J Respir Crit Care Med. 2008;177:1150-1155 [PubMed]journal. [CrossRef] [PubMed]
 
Dean D.A. .Wang R. .Jacobs D.R. .et al A systematic assessment of the association of polysomnographic indices with blood pressure: the Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015;38:587-596 [PubMed]journal. [PubMed]
 
Berry R.B. .Budhiraja R. .Gottlieb D.J. .et al Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. J Clin Sleep Med. 2012;8:597-619 [PubMed]journal. [PubMed]
 
Heinzer R. .Vat S. .Marques-Vidal P. .et al Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3:310-318 [PubMed]journal. [CrossRef] [PubMed]
 
Peppard P.E. .Young T. .Barnet J.H. .Palta M. .Hagen E.W. .Hla K.M. . Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177:1006-1014 [PubMed]journal. [CrossRef] [PubMed]
 
Grimaldi D. .Beccuti G. .Touma C. .Van Cauter E. .Mokhlesi B. . Association of obstructive sleep apnea in rapid eye movement sleep with reduced glycemic control in type 2 diabetes: therapeutic implications. Diabetes Care. 2014;37:355-363 [PubMed]journal. [CrossRef] [PubMed]
 
Chami H.A. .Baldwin C.M. .Silverman A. .et al Sleepiness, quality of life, and sleep maintenance in REM versus non-REM sleep-disordered breathing. Am J Respir Crit Care Med. 2010;181:997-1002 [PubMed]journal. [CrossRef] [PubMed]
 
Weaver T.E. .Maislin G. .Dinges D.F. .et al Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007;30:711-719 [PubMed]journal. [PubMed]
 
Calandra-Buonaura G. .Provini F. .Guaraldi P. .Plazzi G. .Cortelli P. . Cardiovascular autonomic dysfunctions and sleep disorders. Sleep Med Rev. 2015;26:43-56 [PubMed]journal. [PubMed]
 
Cortelli P. .Lombardi C. .Montagna P. .Parati G. . Baroreflex modulation during sleep and in obstructive sleep apnea syndrome. Auton Neurosci. 2012;169:7-11 [PubMed]journal. [CrossRef] [PubMed]
 
O'Connor C. .Thornley K.S. .Hanly P.J. . Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161:1465-1472 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Flow diagram of the MAILES study. MAILES = Men Androgens Inflammation Lifestyle Environment and Stress; REM = rapid eye movement.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Biomedical Characteristics, % (No.), of Study Participants With at Least 30 Min of REM Sleep Overall and by Prevalent and Recent-Onset Hypertension
Table Graphic Jump Location
Table 2 Demographic Characteristics of Participants and by AHI Severity Category Overall and During REM Sleep

AHI = apnea hypopnea index; REM = rapid eye movement; UK = United Kingdom.

Table Graphic Jump Location
Table 3 Sleep Study Characteristics, % (No.), of Study Participants With at Least 30 Min of REM Sleep Overall and by Prevalent and Recent-Onset Hypertension
a Epworth Sleepiness Scale > 10.

TST90 quartiles: 25th, 0.056%; 50th, 0.691%; 75th, 3.874%. ODI 3% quartiles: 25th, 3.7665; 50th, 8.2894; 75th, 16.3338. % total time in supine position quartiles: 25th, 6.82%; 50th, 22.66%; 75th, 43.7%. NREM = non-rapid eye movement; ODI 3% = oxygen desaturation index (≥ 3% desaturation events/h of sleep); TST90 = percentage time of sleep time spent with oxygen saturation < 90%. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
Table 4 Prevalent and Recent-Onset Hypertension, % (No.), in Relation to REM OSA Overall and in Men Without OSA (AHI < 10, AHINREM < 10) and OR, 95% CI for Hypertension Associated With REM OSA Severity
a Adjusted for age, waist circumference, smoking, alcohol, sleep hours, quartiles of percentage time in supine sleep position, AHINREM.
b Adjusted as for first modela without AHINREM.
c Adjusted for baseline age, waist circumference, smoking, alcohol, AHINREM, and weight gain over the follow-up period.
d Adjusted as for third modelc without AHINREM.

P presented for distribution of hypertension across REM OSA categories by χ2 linear by linear association. AHINREM = apnea hypopnea index for non-REM. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
Table 5 Prevalent and Recent-Onset Hypertension, % (No.), in Relation to Severity of OSA and OR, 95% CI for Hypertension Associated With OSA Severity
a Pearson χ2.
b χ2 linear by linear association.
c Adjusted for age, waist circumference, smoking, alcohol, and supine sleep position.
d Adjusted for baseline age, waist circumference, smoking, alcohol, and weight gain over the follow-up period.

See Table 2 legend for expansion of abbreviation.

References

Marin J.M. .Agusti A. .Villar I. .et al Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2169-2176 [PubMed]journal. [PubMed]
 
Peppard P.E. .Young T. .Palta M. .Skatrud J. . Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378-1384 [PubMed]journal. [CrossRef] [PubMed]
 
Nieto F.J. .Young T.B. .Lind B.K. .et al Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;283:1829-1836 [PubMed]journal. [CrossRef] [PubMed]
 
Cohen D.L. .Townsend R.R. . Obstructive sleep apnea and hypertension. J Clin Hypertens. 2013;15:703- [PubMed]journal
 
Torres G. .Sanchez-de-la-Torre M. .Barbe F. . Relationship between OSA and Hypertension. Chest. 2015;148:824-832 [PubMed]journal. [CrossRef] [PubMed]
 
Konecny T. .Kara T. .Somers V.K. . Obstructive sleep apnea and hypertension: an update. Hypertension. 2014;63:203-209 [PubMed]journal. [CrossRef] [PubMed]
 
O'Connor G.T. .Caffo B. .Newman A.B. .et al Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study. Am J Respir Crit Care Med. 2009;179:1159-1164 [PubMed]journal. [CrossRef] [PubMed]
 
Cano-Pumarega I. .Duran-Cantolla J. .Aizpuru F. .et al Obstructive sleep apnea and systemic hypertension: longitudinal study in the general population: the Vitoria Sleep Cohort. Am J Respir Crit Care Med. 2011;184:1299-1304 [PubMed]journal. [CrossRef] [PubMed]
 
Bixler E.O. .Vgontzas A.N. .Lin H.M. .et al Association of hypertension and sleep-disordered breathing. Arch Intern Med. 2000;160:2289-2295 [PubMed]journal. [CrossRef] [PubMed]
 
Fava C. .Dorigoni S. .Dalle Vedove F. .et al Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic review and meta-analysis. Chest. 2014;145:762-771 [PubMed]journal. [CrossRef] [PubMed]
 
Mokhlesi B. .Finn L.A. .Hagen E.W. .et al Obstructive sleep apnea during REM sleep and hypertension. Results of the Wisconsin Sleep Cohort. Am J Respir Crit Care Med. 2014;190:1158-1167 [PubMed]journal. [CrossRef] [PubMed]
 
Mokhlesi B. .Hagen E.W. .Finn L.A. .Hla K.M. .Carter J.R. .Peppard P.E. . Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort. Thorax. 2015;70:1062-1069 [PubMed]journal. [CrossRef] [PubMed]
 
Somers V.K. .Dyken M.E. .Mark A.L. .Abboud F.M. . Sympathetic-nerve activity during sleep in normal subjects. New Engl J Med. 1993;328:303-307 [PubMed]journal. [CrossRef] [PubMed]
 
Findley L.J. .Wilhoit S.C. .Suratt P.M. . Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea. Chest. 1985;87:432-436 [PubMed]journal. [CrossRef] [PubMed]
 
Grant J.F. .Martin S.A. .Taylor A.W. .et al Cohort profile: the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study. Int J of Epidemiol. 2014;43:1040-1053 [PubMed]journal. [CrossRef]
 
Iber C. .Ancoli Israel S. .Chesson A. Jr..Quan S. . The AASM Manual for the Scoring of Sleep and Associated Events.  2007;:- [PubMed] American Academy of Sleep Medicine Westchester, ILjournal
 
ASTA/ASA. Commentary on AASM Manual for the Scoring of Sleep and Associated Events. December 2010.http://www.sleep.org.au/information/sleep-documents/astaasa-commentary-on-aasm-manual-for-scoring-of-sleep-associated-events-december-2010. Accessed December 1, 2016.
 
Ruehland W.R. .Rochford P.D. .O'Donoghue F.J. .Pierce R.J. .Singh P. .Thornton A.T. . The new AASM criteria for scoring hypopneas: impact on the apnea hypopnea index. Sleep. 2009;32:150-157 [PubMed]journal. [PubMed]
 
Mokhlesi B. .Punjabi N.M. . “REM-related” obstructive sleep apnea: an epiphenomenon or a clinically important entity? Sleep. 2012;35:5-7 [PubMed]journal. [PubMed]
 
Lee C.M.Y. .Huxley R.R. .Wildman R.P. .Woodward M. . Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol. 2008;61:646-653 [PubMed]journal. [CrossRef] [PubMed]
 
Peker Y. . REM sleep: a nightmare for patients with obstructive sleep apnea? Am J Respir Crit Care Med. 2014;190:1088-1090 [PubMed]journal. [CrossRef] [PubMed]
 
Punjabi N.M. .Newman A.B. .Young T.B. .Resnick H.E. .Sanders M.H. . Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas. Am J Respir Crit Care Med. 2008;177:1150-1155 [PubMed]journal. [CrossRef] [PubMed]
 
Dean D.A. .Wang R. .Jacobs D.R. .et al A systematic assessment of the association of polysomnographic indices with blood pressure: the Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015;38:587-596 [PubMed]journal. [PubMed]
 
Berry R.B. .Budhiraja R. .Gottlieb D.J. .et al Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. J Clin Sleep Med. 2012;8:597-619 [PubMed]journal. [PubMed]
 
Heinzer R. .Vat S. .Marques-Vidal P. .et al Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3:310-318 [PubMed]journal. [CrossRef] [PubMed]
 
Peppard P.E. .Young T. .Barnet J.H. .Palta M. .Hagen E.W. .Hla K.M. . Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177:1006-1014 [PubMed]journal. [CrossRef] [PubMed]
 
Grimaldi D. .Beccuti G. .Touma C. .Van Cauter E. .Mokhlesi B. . Association of obstructive sleep apnea in rapid eye movement sleep with reduced glycemic control in type 2 diabetes: therapeutic implications. Diabetes Care. 2014;37:355-363 [PubMed]journal. [CrossRef] [PubMed]
 
Chami H.A. .Baldwin C.M. .Silverman A. .et al Sleepiness, quality of life, and sleep maintenance in REM versus non-REM sleep-disordered breathing. Am J Respir Crit Care Med. 2010;181:997-1002 [PubMed]journal. [CrossRef] [PubMed]
 
Weaver T.E. .Maislin G. .Dinges D.F. .et al Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007;30:711-719 [PubMed]journal. [PubMed]
 
Calandra-Buonaura G. .Provini F. .Guaraldi P. .Plazzi G. .Cortelli P. . Cardiovascular autonomic dysfunctions and sleep disorders. Sleep Med Rev. 2015;26:43-56 [PubMed]journal. [PubMed]
 
Cortelli P. .Lombardi C. .Montagna P. .Parati G. . Baroreflex modulation during sleep and in obstructive sleep apnea syndrome. Auton Neurosci. 2012;169:7-11 [PubMed]journal. [CrossRef] [PubMed]
 
O'Connor C. .Thornley K.S. .Hanly P.J. . Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161:1465-1472 [PubMed]journal. [CrossRef] [PubMed]
 
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